Impaired fear processing in right mesial temporal sclerosis: a fMRI study

Lesion and neuroimaging studies have demonstrated that the mesial temporal lobe is crucial for recognizing emotions from facial expressions. In humans, bilateral amygdala damage is followed by impaired recognition of facial expressions of fear. To evaluate the influence of unilateral mesial temporal lobe damage we examined recognition of facial expressions and functional magnetic resonance (fMRI) brain activation associated with incidental processing of fearful faces in thirteen mesial temporal lobe epilepsy (MTLE) patients (eight with right MTLE, five with left MTLE). We also examined the effect of early versus later damage, comparing subjects with hippocampal-amygdalar sclerosis (MTS) and seizures occurring before five years of age to epilepsy patients with late onset seizures. Fourteen healthy volunteers participated as controls. Neuropsychological testing demonstrated that the ability of right MTLE patients to recognize fearful facial expressions is impaired. Patients with early onset of seizures were the most severely impaired. This deficit was associated with defective activation of a neural network involved in the processing of fearful expressions, which in controls and left MTLE included the left inferior frontal cortex and several occipito-temporal structures of both hemispheres.     

Association between structural abnormalities and fMRI response in the amygdala in patients with temporal lobe epilepsy

ObjectiveThe goal of this study was to investigate whether dysplastic amygdalae show an impaired response as revealed by functional MRI (fMRI).MethodsA fearful face fMRI paradigm using video sequences, as we have recently applied, was used in 25 patients with temporal lobe epilepsy (TLE): 24 had mesial TLE (14 right-, nine left-sided, one bilateral); one left lateral neocortical TLE. T1-, T2-weighted and fluid attenuated inversion recovery (FLAIR) MRI sequences were assessed for the detection and categorisation of structural amygdalar abnormalities according to size and MR signal intensity. Of the 25 patients, five patients had probable dysplastic amygdala (pDA): two right- and three left-sided.ResultsA fearful face paradigm led to significant amygdalar activation in all but one patient (p < 0.05). In 15 (60%) of the patients amygdalar activation was found contralateral and in four (16%) ipsilateral to the side of seizure onset. Bilateral amygdalar activation was registered in five (20%) patients. In two patients with right-sided and one with left-sided pDA, fMRI activation was observed only in the contralateral amygdala. In two out of three patients with left-sided pDA we found significant ipislateral amygdalar fMRI-responses.ConclusionUnilateral pDA does not necessarily affect the amygdalar fMRI BOLD-response.     

Patterns of altered functional connectivity in mesial temporal lobe epilepsy

Purpose: In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction. Methods: We selected electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG‐fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated. Key Findings: In patients with right MTLE, group difference functional connectivity maps (RMTLE ? controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE ? controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus. Significance: In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.     

Altered Amygdala Connectivity Within the Social Brain in Schizophrenia

Background: Impairments in social cognition have been described in schizophrenia and relate to core symptoms of the disorder. Social cognition is subserved by a network of brain regions, many of which have been implicated in schizophrenia. We hypothesized that deficits in connectivity between components of this social brain network may underlie the social cognition impairments seen in the disorder. Methods: We investigated brain activation and connectivity in a group of individuals with schizophrenia making social judgments of approachability from faces (n = 20), compared with a group of matched healthy volunteers (n = 24), using functional magnetic resonance imaging. Effective connectivity from the amygdala was estimated using the psychophysiological interaction approach. Results: While making approachability judgments, healthy participants recruited a network of social brain regions including amygdala, fusiform gyrus, cerebellum, and inferior frontal gyrus bilaterally and left medial prefrontal cortex. During the approachability task, healthy participants showed increased connectivity from the amygdala to the fusiform gyri, cerebellum, and left superior frontal cortex. In comparison to controls, individuals with schizophrenia overactivated the right middle frontal gyrus, superior frontal gyrus, and precuneus and had reduced connectivity between the amygdala and the insula cortex. Discussion: We report increased activation of frontal and medial parietal regions during social judgment in patients with schizophrenia, accompanied by decreased connectivity between the amygdala and insula. We suggest that the increased activation of frontal control systems and association cortex may reflect a compensatory mechanism for impaired connectivity of the amygdala with other parts of the social brain networks in schizophrenia.Key words: fMRI, social cognition, approachability, psychosis, neural, psychophysiological interaction     

Functional disconnectivity of the medial temporal lobe in Asperger's syndrome.

BACKGROUND: Autistic spectrum disorders (ASD) are neurodevelopmental conditions that may be caused by abnormal connectivity between brain regions constituting neurocognitive networks for specific aspects of social cognition. METHODS: We used three-way multidimensional scaling of regionally parcellated functional magnetic resonance imaging (fMRI) data to explore the hypothesis of abnormal functional connectivity in people with ASD. Thirteen high-functioning individuals with Asperger's syndrome and 13 healthy volunteers were scanned during incidental processing of fearful facial expressions. RESULTS: Using permutation tests for inference, we found evidence for significant abnormality of functional integration of amygdala and parahippocampal gyrus (p < .05, false discovery rate [FDR] corrected) in people with Asperger's syndrome. There were less salient abnormalities in functional connectivity of anterior cingulate, inferior occipital, and inferior frontal cortex, but there was no significant difference between groups in whole brain functional connectivity. CONCLUSIONS: We conclude there is evidence that functional connectivity of medial temporal lobe structures specifically is abnormal in people with Asperger's syndrome during fearful face processing.     

Brain plasticity for verbal and visual memories in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An fMRI study

We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left‐HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left‐HS group recruited more widespread cortical areas, which were even more widespread in the right‐HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right‐HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Preoperative amygdala fMRI in temporal lobe epilepsy

Purpose:   Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.
Methods:   We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.
Results:   On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.
Discussion:   The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.     

Altered amygdalar resting‐state connectivity in depression is explained by both genes and environment

Recent findings indicate that alterations of the amygdalar resting‐state fMRI connectivity play an important role in the etiology of depression. While both depression and resting‐state brain activity are shaped by genes and environment, the relative contribution of genetic and environmental factors mediating the relationship between amygdalar resting‐state connectivity and depression remain largely unexplored. Likewise, novel neuroimaging research indicates that different mathematical representations of resting‐state fMRI activity patterns are able to embed distinct information relevant to brain health and disease. The present study analyzed the influence of genes and environment on amygdalar resting‐state fMRI connectivity, in relation to depression risk. High‐resolution resting‐state fMRI scans were analyzed to estimate functional connectivity patterns in a sample of 48 twins (24 monozygotic pairs) informative for depressive psychopathology (6 concordant, 8 discordant and 10 healthy control pairs). A graph‐theoretical framework was employed to construct brain networks using two methods: (i) the conventional approach of filtered BOLD fMRI time‐series and (ii) analytic components of this fMRI activity. Results using both methods indicate that depression risk is increased by environmental factors altering amygdalar connectivity. When analyzing the analytic components of the BOLD fMRI time‐series, genetic factors altering the amygdala neural activity at rest show an important contribution to depression risk. Overall, these findings show that both genes and environment modify different patterns the amygdala resting‐state connectivity to increase depression risk. The genetic relationship between amygdalar connectivity and depression may be better elicited by examining analytic components of the brain resting‐state BOLD fMRI signals. Hum Brain Mapp 36:3761–3776, 2015. © 2015 Wiley Periodicals, Inc.     

Widespread grey matter changes and hemodynamic correlates to interictal epileptiform discharges in pharmacoresistant mesial temporal epilepsy

Focal onset epilepsies most often occur in the temporal lobes. To improve diagnosis and therapy of patients suffering from pharmacoresistant temporal lobe epilepsy it is highly important to better understand the underlying functional and structural networks. In mesial temporal lobe epilepsy (MTLE) widespread functional networks are involved in seizure generation and propagation. In this study we have analyzed the spatial distribution of hemodynamic correlates (HC) to interictal epileptiform discharges on simultaneous EEG/fMRI recordings and relative grey matter volume (rGMV) reductions in 10 patients with MTLE. HC occurred beyond the seizure onset zone in the hippocampus, in the ipsilateral insular/operculum, temporo-polar and lateral neocortex, cerebellum, along the central sulcus and bilaterally in the cingulate gyrus. rGMV reductions were detected in the middle temporal gyrus, inferior temporal gyrus and uncus to the hippocampus, the insula, the posterior cingulate and the anterior lobe of the cerebellum. Overlaps between HC and decreased rGMV were detected along the mesolimbic network ipsilateral to the seizure onset zone. We conclude that interictal epileptic activity in MTLE induces widespread metabolic changes in functional networks involved in MTLE seizure activity. These functional networks are spatially overlapping with areas that show a reduction in relative grey matter volumes.     

Sex differences in amygdala activation during the perception of facial affect

The cognitive and affective systems of the cerebral cortex are often more lateralized in males than females, but it is unclear whether these differences extend to subcortical systems. We used fMRI to examine sex differences in lateralized amygdala activity during happy and fearful face perception. Amygdala activation differed for men and women depending on the valence of the expression. Overall, males were more lateralized than females, but the direction differed between valence conditions. Happy faces produced greater right than left amygdala activation for males but not females. Both sexes showed greater left amygdala activation for fearful faces. These findings suggest that the lateralization of affective function may extend beyond the cortex to subcortical regions such as the amygdala.     

Abnormal superior temporal connectivity during fear perception in schizophrenia

Patients with schizophrenia have difficulty in decoding facial affect. A study using event-related functional neuroimaging indicated that errors in fear detection in schizophrenia are associated with paradoxically higher activation in the amygdala and an associated network implicated in threat detection. Furthermore, this exaggerated activation to fearful faces correlated with severity of flat affect. These findings suggest that abnormal threat detection processing may reflect disruptions between nodes that comprise the affective appraisal circuit. Here we examined connectivity within this network by determining the pattern of intercorrelations among brain regions (regions of interest) significantly activated during fear identification in both healthy controls and patients using a novel procedure CORANOVA. This analysis tests differences in the interregional correlation strength between schizophrenia and healthy controls. Healthy subjects' task activation was principally characterized by robust correlations between medial structures like thalamus (THA) and amygdala (AMY) and middle frontal (MF), inferior frontal (IF), and prefrontal cortical (PFC) regions. In contrast, schizophrenia patients displayed no significant correlations between the medial regions and either MF or IF. Further, patients had significantly higher correlations between occipital lingual gyrus and superior temporal gyrus than healthy subjects. These between-group connectivity differences suggest that schizophrenia threat detection impairment may stem from abnormal stimulus integration. Such abnormal integration may disrupt the evaluation of threat within fronto-cortical regions.     

Lesion side matters — An fMRI study on the association between neural correlates of watching dynamic fearful faces and their evaluation in patients with temporal lobe epilepsy

Most studies assessing facial affect recognition in patients with TLE reported emotional disturbances in patients with TLE. Results from the few fMRI studies assessing neural correlates of affective face processing in patients with TLE are divergent. Some, but not all, found asymmetrical mesiotemporal activations, i.e., stronger activations within the hemisphere contralateral to seizure onset. Little is known about the association between neural correlates of affect processing and subjective evaluation of the stimuli presented. Therefore, we investigated the neural correlates of processing dynamic fearful faces in 37 patients with mesial temporal lobe epilepsy (TLE; 18 with left-sided TLE (lTLE), 19 with right-sided TLE (rTLE)) and 20 healthy subjects. We additionally assessed individual ratings of the fear intensity and arousal perception of the fMRI stimuli and correlated these data with the activations induced by the fearful face paradigm and activation lateralization within the mesiotemporal structures (in terms of individual lateralization indices, LIs). In healthy subjects, whole-brain analysis showed bilateral activations within a widespread network of mesial and lateral temporal, occipital, and frontal areas. The patient groups activated different parts of this network. In patients with lTLE, we found predominantly right-sided activations within the mesial and lateral temporal cortices and the superior frontal gyrus. In patients with rTLE, we observed bilateral activations in the posterior regions of the lateral temporal lobe and within the occipital cortex. Mesiotemporal region-of-interest analysis showed bilateral symmetric activations associated with watching fearful faces in healthy subjects. According to the region of interest and LI analyses, in the patients with lTLE, mesiotemporal activations were lateralized to the right hemisphere. In the patients with rTLE, we found left-sided mesiotemporal activations. In patients with lTLE, fear ratings were comparable to those of healthy subjects and were correlated with relatively stronger activations in the right compared to the left amygdala. Patients with rTLE showed significantly reduced fear ratings compared to healthy subjects, and we did not find associations with amygdala lateralization. Although we found stronger activations within the contralateral mesial temporal lobe in the majority of all patients, our results suggest that only in the event of left-sided mesiotemporal damage is the right mesial temporal lobe able to preserve intact facial fear recognition. In the event of right-sided mesiotemporal damage, fear recognition is disturbed. This underlines the hypothesis that the right amygdala is biologically predisposed to processing fear, and its function cannot be fully compensated in the event of right-sided mesiotemporal damage.     

Extratemporal functional connectivity impairments at rest are related to memory performance in mesial temporal epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of focal epilepsy. At rest, there is evidence that brain abnormalities in MTLE are not limited to the epileptogenic region, but extend throughout the whole brain. It is also well established that MTLE patients suffer from episodic memory deficits. Thus, we investigated the relation between the functional connectivity seen at rest in fMRI and episodic memory impairments in MTLE. We focused on resting state BOLD activity and evaluated whether functional connectivity (FC) differences emerge from MTL seeds in left and right MTLE groups, compared with healthy controls. Results revealed significant FC reductions in both patient groups, localized in angular gyri, thalami, posterior cingulum and medial frontal cortex. We found that the FC between the left non‐pathologic MTL and the medial frontal cortex was positively correlated with the delayed recall score of a non‐verbal memory test in right MTLE patients, suggesting potential adaptive changes to preserve this memory function. In contrast, we observed a negative correlation between a verbal memory test and the FC between the left pathologic MTL and posterior cingulum in left MTLE patients, suggesting potential functional maladaptative changes in the pathologic hemisphere. Overall, the present study provides some indication that left MTLE may be more impairing than right MTLE patients to normative functional connectivity. Our data also indicates that the pattern of extra‐temporal FC may vary as a function of episodic memory material and each hemisphere's capacity for cognitive reorganization. Hum Brain Mapp 34:2202–2216, 2013. © 2012 Wiley Periodicals, Inc.     

Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures

Background It has been hypothesised that seizure induced neuronal loss and axonal damage in medial temporal lobe epilepsy (MTLE) may lead to the development of aberrant connections between limbic structures and eventually result in the reorganisation of the limbic network. In this study, limbic structural connectivity in patients with MTLE was investigated, using diffusion tensor MRI, probabilistic tractography and graph theory based network analysis. Methods 12 patients with unilateral MTLE and hippocampal sclerosis (five left and seven right MTLE) and 26 healthy controls were studied. The connectivity of 10 bilateral limbic regions of interest was mapped with probabilistic tractography, and the probabilistic fibre density between each pair of regions was used as the measure of their weighted structural connectivity. Binary connectivity matrices were then obtained from the weighted connectivity matrix using a range of fixed density thresholds. Graph theory based properties of nodes (degree, local efficiency, clustering coefficient and betweenness centrality) and the network (global efficiency and average clustering coefficient) were calculated from the weight and binary connectivity matrices of each subject and compared between patients and controls. Results MTLE was associated with a regional reduction in fibre density compared with controls. Paradoxically, patients exhibited (1) increased limbic network clustering and (2) increased nodal efficiency, degree and clustering coefficient in the ipsilateral insula, superior temporal region and thalamus. There was also a significant reduction in clustering coefficient and efficiency of the ipsilateral hippocampus, accompanied by increased nodal degree. Conclusions These results suggest that MTLE is associated with reorganisation of the limbic system. These results corroborate the concept of MTLE as a network disease, and may contribute to the understanding of network excitability dynamics in epilepsy and MTLE.     

Atypical frontal-posterior synchronization of Theory of Mind regions in autism during mental state attribution

This study used fMRI to investigate the functioning of the Theory of Mind (ToM) cortical network in autism during the viewing of animations that in some conditions entailed the attribution of a mental state to animated geometric figures. At the cortical level, mentalizing (attribution of metal states) is underpinned by the coordination and integration of the components of the ToM network, which include the medial frontal gyrus, the anterior paracingulate, and the right temporoparietal junction. The pivotal new finding was a functional underconnectivity (a lower degree of synchronization) in autism, especially in the connections between frontal and posterior areas during the attribution of mental states. In addition, the frontal ToM regions activated less in participants with autism relative to control participants. In the autism group, an independent psychometric assessment of ToM ability and the activation in the right temporoparietal junction were reliably correlated. The results together provide new evidence for the biological basis of atypical processing of ToM in autism, implicating the underconnectivity between frontal regions and more posterior areas.     

Visual Hallucinations Are Associated With Hyperconnectivity Between the Amygdala and Visual Cortex in People With a Diagnosis of Schizophrenia

Introduction:

While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH.

Methods:

We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory).

Results:

Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal pole and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting.

Conclusions:

VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia.     

Large‐scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large‐scale RSNs is differently affected in patients with right‐ and left‐MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting‐state functional‐MRIs of 99 subjects (52 controls, 26 right‐ and 21 left‐MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF²C‐toolbox, which provided ROI‐wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right‐MTLE. Both groups showed abnormal correlation between the dorsal‐DMN and the posterior salience, as well as between the dorsal‐DMN and the executive‐control network. Patients with left‐MTLE also showed reduced correlation between the dorsal‐DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left‐MTLE expressed a low cluster coefficient, whereas the altered connections on right‐MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right‐ and left‐MTLE patients with HS have widespread abnormal interactions of large‐scale brain networks; however, all parameters evaluated indicate that left‐MTLE has a more intricate bihemispheric dysfunction compared to right‐MTLE. Hum Brain Mapp 37:3137–3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Cerebral activation patterns during working memory performance in multiple sclerosis using FMRI

Working memory deficits are common in Multi Sclerosis (MS) and have been identified behaviourally in numerous studies. Despite recent advance in functional magnetic resonance imaging (fMRI), few published studies have examined cerebral activations associated with working memory dysfunction in MS. The present study examines brain activation patterns during performance of a working memory task in individual with clinically definite MS, compared to healthy controls (HC). fMRI was performed using a 1.5 Tesla GE scanner during a modified Paced Auditory Serial Addition Test (mPA-SAT). Participants were 6 individuals with MS with working memory impairment as evidenced on neuropsychological testing, 5 individuals with MS without working memory impairment, and 5 HC. Groups were demographically equivalent. Data were analyzed using Statistical Parametric Mapping (SPM99) software, with a stringent significance level (alpha < .005, voxel extent > or =8). Both MS groups and the HC group were able to perform the task, with comparable performance in terms of numbers of correct responses. Activation patterns within the HC and MS not-impaired groups were noted in similar brain regions, consistent with published observations in healthy samples That is, activations were lateralized to the left hemisphere, involving predominantly frontal regions. In contrast, the MS impaired group showed greater right frontal and right parietal lobe activation, when compared with the HC group. Thus, it appears that working memory dysfunction in MS is associated with altered patterns of cerebral activation that are related to the presence of cognitive impairement, and not solely a function of MS.     

Distributed and interactive brain mechanisms during emotion face perception: evidence from functional neuroimaging

Brain imaging studies in humans have shown that face processing in several areas is modulated by the affective significance of faces, particularly with fearful expressions, but also with other social signals such gaze direction. Here we review haemodynamic and electrical neuroimaging results indicating that activity in the face-selective fusiform cortex may be enhanced by emotional (fearful) expressions, without explicit voluntary control, and presumably through direct feedback connections from the amygdala. fMRI studies show that these increased responses in fusiform cortex to fearful faces are abolished by amygdala damage in the ipsilateral hemisphere, despite preserved effects of voluntary attention on fusiform; whereas emotional increases can still arise despite deficits in attention or awareness following parietal damage, and appear relatively unaffected by pharmacological increases in cholinergic stimulation. Fear-related modulations of face processing driven by amygdala signals may implicate not only fusiform cortex, but also earlier visual areas in occipital cortex (e.g., V1) and other distant regions involved in social, cognitive, or somatic responses (e.g., superior temporal sulcus, cingulate, or parietal areas). In the temporal domain, evoked-potentials show a widespread time-course of emotional face perception, with some increases in the amplitude of responses recorded over both occipital and frontal regions for fearful relative to neutral faces (as well as in the amygdala and orbitofrontal cortex, when using intracranial recordings), but with different latencies post-stimulus onset. Early emotional responses may arise around 120ms, prior to a full visual categorization stage indexed by the face-selective N170 component, possibly reflecting rapid emotion processing based on crude visual cues in faces. Other electrical components arise at later latencies and involve more sustained activities, probably generated in associative or supramodal brain areas, and resulting in part from the modulatory signals received from amygdala. Altogether, these fMRI and ERP results demonstrate that emotion face perception is a complex process that cannot be related to a single neural event taking place in a single brain regions, but rather implicates an interactive network with distributed activity in time and space. Moreover, although traditional models in cognitive neuropsychology have often considered that facial expression and facial identity are processed along two separate pathways, evidence from fMRI and ERPs suggests instead that emotional processing can strongly affect brain systems responsible for face recognition and memory. The functional implications of these interactions remain to be fully explored, but might play an important role in the normal development of face processing skills and in some neuropsychiatric disorders.